The Radiation Therapy Oncology Group (RTOG), formed 20 years ago and now under new leadership, is a carefully structured cooperative association of physician, physicists, biologists, and biostatisticians who pursue clinical investigations to increase cure and improve palliation of patients with cancer. Radiation therapy is a highly effective modality which is used for more than half the cancer patients in the United Stats: half of these are treated with curative intent and fully half are cured. Radiation therapy is an important part of most, but not all, of the investigations of the RTOG. Improvements in local-regional control are central to many studies, but prevention or treatment of distant metastasis is also sought. Assessments of clinical failure patterns have influenced the research strategies of the Group - whether to emphasize local, regional or distant treatments Concepts developed from laboratory research have consistently been transferred into clinical trials: this integration of basic biologic and clinical investigations is a hallmark of the RTOG. Cellular and molecular studies have pointed to the importance of hypoxia and inherent resistance in local tumors: accelerated proliferation may relate both to local and distant manifestations. RTOG strategies have emphasized hypoxic cell sensitizers, hyperthermia and cytotoxic chemotherapy as adjuncts to radiation therapy, and alterations of fractionation, to overcome these mechanisms of resistance. Surgery, alone and with intraoperative radiation therapy and chemical modifiers other than those hypoxia- directed, represent important local regional efforts, while systemic chemotherapy and radiolabelled antibodies address local and distant disease compartments. All of these modalities may be used in phase I/II trials; promising results lead to phase III trials of the RTOG or intergroup studies. Five disease sites -head and neck, lung, brain, prostate and cervix - are subject to phase III study within the RTOG; other sites require intergroup collaboration. Structurally, the RTOG has expanded the participation of medical and surgical oncologists and pathologists, and further integrated basic biologic and clinical investigations. Core Laboratories are being developed by pathologists and biologists to study flow cytometry, hypoxic cells, and inherent resistance. New investigators have strengthened the group and major institutions have joined. Refinement of he research strategies to achieve the most effective application of the several unique modalities of the RTOG to the most appropriate disease sites, should permit an expanded level of participation with increased accrual to studies that will hasten the conquest of cancer.